Studies of the binding of sex steroids, particularly of estradiol by human serum in normal and cancer patients, are being carried out. With the use of a new method for the measurement of percentage of free steroid under physiologic conditions, it has been shown that variations in the serum concentration of sex hormone binding globulin (SHBG) lead to inverse changes in the percentage of free estradiol. For example, the level of SHBG is severely depressed in obese subjects which leads to a 2-3 fold elevation in the percentage of free estradiol which may be of etiologic significance in endometrial and breast cancer. In addition, some women with breast cancer have an elevated percentage of free estradiol despite normal SHBG levels suggesting abnormalities in the binding reaction arising from changes in the protein or the presence of competitive inhibitors. Additional studies have shown that the metabolic clearance rates of each of 12 steroids are inversely proportional to the percentage that is bound to the high affinity binders SHBG or CBG.